Various publications, including patents, published applications and scholarly articles, are cited throughout the specification. Each of these publications is incorporated by reference herein, in its entirety.
Therapeutic agents delivered in a conventional or non-specific manner often are distributed to non-designated areas of the body. As a consequence, the agent may be metabolized, for example, through first pass metabolism of the liver, thereby resulting in diminished bioavailability and the possibility for increased dosing at a higher cost and with the risk of adverse side effects. In addition, non-specific distribution of therapeutic agents may result in adverse effects and unwanted pharmacological responses in the subject to which they are administered. As a result, certain agents may be contraindicated in certain subjects or under certain conditions.
Implanting medical devices within a subject may necessitate follow-up chemotherapy, for example, to lessen the possibility for infection, to reduce inflammation, to repair tissue, or to prevent further local tissue damage. Drug-eluting devices, including stents, are increasingly used in a variety of biomedical applications to effectuate targeted delivery of drugs to the area of the implant. Drug-containing implants are limited, however, insofar as they generally contain only a small dose of a single therapeutic agent, and therefore lack the possibility for re-administration of the same or different therapeutic agent through the implanted device.
Nanoparticles and microparticles have shown potential as carrier systems for a variety of therapeutic agents, including enzymes for enzyme replacement therapy, hormones, cell modifying agents and genetic material as well as for imaging. Initial attempts to use nanoparticles and microparticles for site-specific delivery have shown potential to lower adverse effects in the patients to which they are administered, attributed in part to lower doses of therapeutic agents being required.
The foregoing discussion indicates that carrier systems show promise for optimizing agent administration, and as a possible vehicle for targeted drug delivery. Such technology is limited, however, in its capacity to actually effectuate optimized targeted delivery. In this regard, magnet targeting is considered an attractive way to achieve optimized targeted delivery of agents, particularly those formulated as a nanoparticle carrier. Preliminary attempts to deliver magnetized therapeutic agents or agent-containing magnetic carriers to specific locations in the body have shown promise, see U.S. Pat. No. 5,921,244. These methodologies, however, suffer from a major drawback, namely that this approach is restricted to targets that are close to the surface of the body.
Thus, a need exists for an optimized and efficacious targeting using magnetic carriers. It is desired that therapeutic systems allow for peripheral as well as local administration, and that the therapeutic system allow practitioners to administer doses of agents that lessen untoward effects in patients, as well as allow administration of agents to patients in situations where they may otherwise be contraindicated due to the possibility of non-specific distribution or of high dose requirements. There is a further need to be able to remove unused or spent magnetic carriers to further lessen the possibility for untoward effects on the patient. The present invention addresses these and other long felt needs.